Poor regeneration and reconnection of retinal ganglion cell (RGC) axons is a major obstacle for treating ocular trauma and diseases including glaucoma. There are as yet no therapies to repair optic nerve once the damage is done. Our new studies now demonstrate that simultaneous manipulation of multiple molecules specifically in RGCs using adeno-associated virus vectors promotes long distance optic nerve regeneration in mice. Furthermore, we now demonstrate improved axon pathfinding and re-innervation of RGC axons using local expression of chemoattractants. In Aim 1, we will use transgenic mice and electron microscopy to examine whether these axons in fact form synapses. In Aim 2, we will examine strategies to further improve target re-innervation. In Aim 3, we will examine whether the manipulated RGCs show normal or altered physiology. Identifying methods to further increase regeneration to brain and determining whether the regenerated axons restore visual functions represent critical future studies. Results obtained from these studies will provid invaluable information on developing future therapies to repair degenerated optic nerve.